In the field of oncology, it is well recognized that a decrease in mass, density, strength, or function of skeletal muscle is associated to increased treatment toxicities and postoperative complications, as well as poor progression-free survival and overall survival. The ability of amino acids to stimulate protein synthesis in cancer patients is reduced. Considering nutritional intervention, this anabolic resistance could be in a part counteracted by increasing protein or by giving specific amino acids. In particular, Leucine might counteract this anabolic resistance not only by increasing substrate availability, but also by directly modulating the anabolic signal pathway...

BACKGROUND: Citrulline (CIT), is not extracted by the splanchnic area, can stimulate muscle protein synthesis and could potentially find clinical applications in conditions involving low amino acid (AA) intake, such as in malnourished older subjects. OBJECTIVE: Our purpose was to research the effects of CIT supplementation on protein metabolism in particular on non-oxidative leucine disposal (NOLD, primary endpoint), and splanchnic extraction of amino acids in malnourished older patients...

The extracellular matrix (ECM) plays key roles in normal and diseased skeletal and cardiac muscle. In healthy muscle the ECM is essential for transmitting contractile force, maintaining myofiber integrity and orchestrating cellular signaling. Duchenne Muscular Dystrophy (DMD) is caused by loss of dystrophin, a cytosolic protein that anchors a transmembrane complex and serves as a vital link between the actin cytoskeleton and the basal lamina. Loss of dystrophin leads to membrane fragility and impaired signaling, resulting in myofiber death and cycles of inflammation and regeneration...

Background: For infants born moderately/late preterm (32-37 weeks of gestation), immaturity of the intestine has the potential to impact both short- and long-term gastrointestinal function. The aim of this study conducted in sheep was to compare the morphology and smooth muscle contractility of the ileum in term and late preterm lambs. Materials and methods: Lambs delivered preterm (132 days gestation; n = 7) or term (147 days gestation; n = 9) were milk-fed after birth and euthanased at 2 days of age...

PURPOSE: The responsiveness of older individuals' skeletal muscle to anabolic strategies may be impaired. However, direct comparisons within the same experimental setting are sparse. The aim of this study was to assess the resting and post-resistance exercise muscle protein synthesis rates in response to two types of milk protein and carbohydrate using a unilateral exercise leg model. METHODS: Twenty-seven older (69 ± 1 year, mean ± SE) men were randomly assigned one of three groups: Whey hydrolysate (WH), caseinate (CAS), or carbohydrate (CHO)...

Leucine has been shown to stimulate the mammalian/mechanistic target of rapamycin (mTOR) signaling pathway which plays numerous key regulatory roles in cell growth, survival and metabolism including protein synthesis in a number of species. However, previous work with equine satellite cells has suggested distinct species differences in regards to physiological effects and the magnitude of responses to growth factors and regulators. Because there is limited research available regarding the role of leucine in regulating equine skeletal muscle protein synthesis, the objective of this study was to evaluate the effect of leucine on the mTOR signaling pathway in cultured equine satellite...

Mammalian target of rapamycin (mTOR) signaling controls skeletal muscle cell differentiation, growth, and metabolism by sensing the intracellular energy status and nutrients. Recently, leucyl-tRNA synthetase (Lars) was identified as an intracellular sensor of leucine involved in the activation of mTOR signaling. However, there is still no evidence for the activation of mTOR signaling by Lars and its physiological roles in skeletal muscle cells. In this study, we determined the potential roles of Lars for the activation of mTOR signaling, skeletal muscle cell differentiation, hypertrophy, and metabolism using small interfering (si)-RNA knockdown...

Skeletal muscle supports locomotion and serves as the largest site of postprandial glucose disposal; thus it is a critical organ for physical and metabolic health. Skeletal muscle mass is regulated by the processes of muscle protein synthesis (MPS) and muscle protein breakdown (MPB), both of which are sensitive to external loading and aminoacidemia. Hyperaminoacidemia results in a robust but transient increase in rates of MPS and a mild suppression of MPB. Resistance exercise potentiates the aminoacidemia-induced rise in MPS that, when repeated over time, results in gradual radial growth of skeletal muscle (i...

Adapter protein containing PH domain, PTB domain, and leucine zipper motif 1 (APPL1) has been reported as a positive regulator of insulin-stimulated Akt activation. The expression of APPL1 is reduced in skeletal muscles of type 2 diabetic (T2D) animals, implying that APPL1 may be an important factor affecting insulin sensitivity. However, the regulation of APPL1 expression and the physiological interventions modulating these effects are unclear. Accordingly, we first confirmed that APPL1 expression and Akt phosphorylation were significantly attenuated in skeletal muscles of T2D rats...

PURPOSE OF REVIEW: β-Hydroxy β-methylbutyrate (HMB) has been used for many years in athletes for muscle buildup and strength, and endurance enhancement. In recent years, its interest quickly expanded in older (diseased) populations and during (exercise) rehabilitation and recovery from hospitalization and surgery. We will discuss recent literature about HMB metabolism, its pharmacokinetics compared with the frequently used metabolite leucine, effectiveness of HMB to improve outcome in older diseased adults, and novel approaches for HMB use...

Muscle fructose 1,6-bisphosphatase (FBP2), besides being a regulatory enzyme of glyconeogenesis also protects mitochondria against calcium stress and plays a key role in regulation of the cell cycle, promoting cardiomyocytes survival. However, in cancer cells, FBP2 acts as an anti-oncogenic/anti-proliferative protein. Here, we show that the physiological function of FBP2 depends both on its level of expression in a cell as well as its oligomerization state. Animal fructose-1,6-bisphosphatases are thought to function as tetramers...

Senegalese sole is one of the most promising fish species cultivated in the Southern European countries. This study was aimed at assessing the effects of microalgae biomass added to diets for Senegalese sole juveniles on fish growing and condition status. Three isoproteic (52%) and isolipidic (10%) were formulated containing 15% Tisochrysis lutea (TISO), Nannochloropsis gaditana (NAN), or Scenedesmus almeriensis (SCE) biomass, respectively. An experimental microalgae-free diet (CT) and a commercial diet (COM) were used as controls...

BACKGROUND: Sarcopenia (the age-related loss of muscle mass and function) is a major contributor to loss of mobility, falls, loss of independence, morbidity and mortality in older people. Although resistance training is effective in preventing and reversing sarcopenia, many older people are sedentary and either cannot or do not want to exercise. This trial examines the efficacy of supplementation with the amino acid leucine and/or angiotensin converting enzyme inhibition to potentially improve muscle mass and function in people with sarcopenia...

Regulation of nutrient intake, utilization, and storage exhibits a circadian rhythmicity that allows organisms to anticipate and adequately respond to changes in the environment across day/night cycles. The branched-chain amino acids (BCAAs) leucine, isoleucine, and valine are important modulators of metabolism and metabolic health - for example, their catabolism yields carbon substrates for gluconeogenesis during periods of fasting. Krüppel-like factor 15 (KLF15) has recently emerged as a critical transcriptional regulator of BCAA metabolism, and the absence of this transcription factor contributes to severe pathologies such as Duchenne muscular dystrophy and heart failure...

Fatigue is a common and serious health problem, and various dietary interventions have previously been employed to ameliorate fatigue. The aim of the current study was to investigate the anti‑fatigue effects of Danish porcine placenta (DPP) and its major dipeptides, including leucine‑glycine (LG) and glycine‑leucine (GL). The anti‑fatigue effects of orally administered DPP, LG and GL were determined using a treadmill exercise test and a forced swimming test (FST) in mice. Additionally, the anti‑inflammatory effects of DPP, LG and GL were investigated in activated splenocytes...